Functional and mechanistic study of miR-148a-3p as a novel biomarker for type 2 diabetic peripheral neuropathy

Type 2 diabetic peripheral neuropathy (T2DM-DPN) not only raises amputation risk but also strains healthcare resources, making the identification of diagnostic biomarkers crucial for early intervention and targeted treatment.

The research sought to examine the expression levels, functional significance, and regulatory mechanisms of miR-148a-3p in the context of T2DM-DPN.

Serum from T2DM patients was collected to assess miR-148a-3p levels and its association with DPN. In vitro, high glucose (HG) cells underwent CCK-8, flow cytometry, and ELISA to examine miR-148a-3p's effects on proliferation, apoptosis, and inflammation. Bioinformatics predicted miR-148a-3p targets, with PTEN regulation confirmed by dual-luciferase assays.

The expression of miR-148a-3p was markedly decreased in T2DM-DPN patients. ROC curve analysis demonstrated its diagnostic value for distinguishing DPN from non-DPN cases (AUC = 0.916), and multivariate analysis identified it as an independent risk factor for T2DM-DPN. In vitro experiments confirmed that miR-148a-3p could counteract high glucose-induced suppression of cell proliferation, promotion of apoptosis and pro-inflammatory effects. Gene Ontology analysis revealed enrichment of miR-148a-3p target genes in biological processes including axon development, angiogenesis, synaptic transmission, and transcriptional regulation. Protein-protein interaction network analysis identified PTEN as a central hub target, and dual-luciferase reporter assays further confirmed that miR-148a-3p directly targets and regulates PTEN.

miR-148a-3p serves as a diagnostic biomarker and therapeutic target for T2DM-DPN by ameliorating hyperglycemia-induced cellular damage through direct PTEN suppression and modulation of neurovascular pathways.